rs10813923

Positions:

• chr9-33023519-G-A
• chr9-33023519-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368995.1(APTX):​c.-5+1481C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,258 control chromosomes in the GnomAD database, including 1,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1312 hom., cov: 33)
• Consequence: APTX NM_001368995.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

Genes affected

APTX (HGNC:15984): (aprataxin) This gene encodes a member of the histidine triad (HIT) superfamily. The encoded protein may play a role in single-stranded DNA repair through its nucleotide-binding activity and its diadenosine polyphosphate hydrolase activity. Mutations in this gene have been associated with ataxia-ocular apraxia. Alternatively spliced transcript variants have been identified for this gene.[provided by RefSeq, Aug 2010]

APTX (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APTX	NM_001368995.1	c.-5+1481C>T		intron_variant			NP_001355924.1
APTX	NM_001368996.1	c.-5+1504C>T		intron_variant			NP_001355925.1
APTX	NM_001368997.1	c.-5+1285C>T		intron_variant			NP_001355926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000468275.6	c.-5+1285C>T		intron_variant		1		ENSP00000420263.2
APTX	ENST00000436040.7	c.-5+1504C>T		intron_variant		1		ENSP00000400806.4
APTX	ENST00000460940.6	n.-5+1481C>T		intron_variant		1		ENSP00000418311.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18812 AN: 152140 Hom.: 1311 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18823 AN: 152258 Hom.: 1312 Cov.: 33 AF XY: 0.124 AC XY: 9261 AN XY: 74452

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.101

Alfa AF: 0.112 Hom.: 454

Bravo AF: 0.123

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10813923; hg19: chr9-33023517;